Molecular analysis of a male breast cancer patient with prolonged stable disease under mTOR/PI3K inhibitors BEZ235/everolimus
Identifieur interne : 000257 ( Ncbi/Merge ); précédent : 000256; suivant : 000258Molecular analysis of a male breast cancer patient with prolonged stable disease under mTOR/PI3K inhibitors BEZ235/everolimus
Auteurs : A. Rose Brannon [États-Unis] ; Melissa Frizziero [Italie] ; David Chen [États-Unis] ; Jennifer Hummel [États-Unis] ; Jorge Gallo [États-Unis] ; Markus Riester [États-Unis] ; Parul Patel [États-Unis] ; Wing Cheung [États-Unis] ; Michael Morrissey [États-Unis] ; Carmine Carbone [Italie] ; Silvia Cottini [Italie] ; Giampaolo Tortora [Italie] ; Davide Melisi [Italie]Source :
- Cold Spring Harbor Molecular Case Studies [ 2373-2865 ] ; 2016.
Abstract
The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER+/HER2− metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR+)/HER2− stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy. Upon the development of metastases, the patient began a 200 mg twice-daily BEZ235 and 2.5 mg weekly everolimus combination regimen. The patient sustained a prolonged stable disease of 18 mo while undergoing the therapy, before his tumor progressed again. Therefore, we sought to both better understand MBC and investigate the underlying molecular mechanisms of the patient's sensitivity and subsequent resistance to the BEZ235/everolimus combination therapy. Genomic and immunohistochemical analyses were performed on samples collected from the initial invasive ductal carcinoma pretreatment and a metastasis postprogression on the BEZ235/everolimus combination treatment. Both tumors were relatively quiet genomically with no overlap to recurrent MBC alterations in the literature. Markers of PI3K/mTOR pathway hyperactivation were not identified in the pretreatment sample, which complements previous reports of HR+ female breast cancers being responsive to mTOR inhibition without this activation. The postprogression sample, however, demonstrated greater than fivefold increased estrogen receptor and pathogenesis-related protein expression, which could have constrained the PI3K/mTOR pathway inhibition by BEZ235/everolimus. Overall, these analyses have augmented the limited episteme on MBC genetics and treatment.
Url:
DOI: 10.1101/mcs.a000620
PubMed: 27148582
PubMed Central: 4849849
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<front><div type="abstract" xml:lang="en"><p>The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER<sup>+</sup>
/HER2<sup>−</sup>
metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR<sup>+</sup>
)/HER2<sup>−</sup>
stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy. Upon the development of metastases, the patient began a 200 mg twice-daily BEZ235 and 2.5 mg weekly everolimus combination regimen. The patient sustained a prolonged stable disease of 18 mo while undergoing the therapy, before his tumor progressed again. Therefore, we sought to both better understand MBC and investigate the underlying molecular mechanisms of the patient's sensitivity and subsequent resistance to the BEZ235/everolimus combination therapy. Genomic and immunohistochemical analyses were performed on samples collected from the initial invasive ductal carcinoma pretreatment and a metastasis postprogression on the BEZ235/everolimus combination treatment. Both tumors were relatively quiet genomically with no overlap to recurrent MBC alterations in the literature. Markers of PI3K/mTOR pathway hyperactivation were not identified in the pretreatment sample, which complements previous reports of HR<sup>+</sup>
female breast cancers being responsive to mTOR inhibition without this activation. The postprogression sample, however, demonstrated greater than fivefold increased estrogen receptor and pathogenesis-related protein expression, which could have constrained the PI3K/mTOR pathway inhibition by BEZ235/everolimus. Overall, these analyses have augmented the limited episteme on MBC genetics and treatment.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="A Hern, Rp" uniqKey="A Hern R">RP A'Hern</name>
</author>
<author><name sortKey="Jamal Hanjani, M" uniqKey="Jamal Hanjani M">M Jamal-Hanjani</name>
</author>
<author><name sortKey="Szasz, Am" uniqKey="Szasz A">AM Szasz</name>
</author>
<author><name sortKey="Johnston, Sr" uniqKey="Johnston S">SR Johnston</name>
</author>
<author><name sortKey="Reis Filho, Js" uniqKey="Reis Filho J">JS Reis-Filho</name>
</author>
<author><name sortKey="Roylance, R" uniqKey="Roylance R">R Roylance</name>
</author>
<author><name sortKey="Swanton, C" uniqKey="Swanton C">C Swanton</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Baselga, J" uniqKey="Baselga J">J Baselga</name>
</author>
<author><name sortKey="Campone, M" uniqKey="Campone M">M Campone</name>
</author>
<author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name>
</author>
<author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Sahmoud, T" uniqKey="Sahmoud T">T Sahmoud</name>
</author>
<author><name sortKey="Noguchi, S" uniqKey="Noguchi S">S Noguchi</name>
</author>
<author><name sortKey="Gnant, M" uniqKey="Gnant M">M Gnant</name>
</author>
<author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name>
</author>
<author><name sortKey="Lebrun, F" uniqKey="Lebrun F">F Lebrun</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bendell, Jc" uniqKey="Bendell J">JC Bendell</name>
</author>
<author><name sortKey="Kurkjian, C" uniqKey="Kurkjian C">C Kurkjian</name>
</author>
<author><name sortKey="Infante, Jr" uniqKey="Infante J">JR Infante</name>
</author>
<author><name sortKey="Bauer, Tm" uniqKey="Bauer T">TM Bauer</name>
</author>
<author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
<author><name sortKey="Greco, Fa" uniqKey="Greco F">FA Greco</name>
</author>
<author><name sortKey="Shih, Kc" uniqKey="Shih K">KC Shih</name>
</author>
<author><name sortKey="Thompson, Ds" uniqKey="Thompson D">DS Thompson</name>
</author>
<author><name sortKey="Lane, Cm" uniqKey="Lane C">CM Lane</name>
</author>
<author><name sortKey="Finney, Lh" uniqKey="Finney L">LH Finney</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bosch, A" uniqKey="Bosch A">A Bosch</name>
</author>
<author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name>
</author>
<author><name sortKey="Bergamaschi, A" uniqKey="Bergamaschi A">A Bergamaschi</name>
</author>
<author><name sortKey="Ellis, H" uniqKey="Ellis H">H Ellis</name>
</author>
<author><name sortKey="Toska, E" uniqKey="Toska E">E Toska</name>
</author>
<author><name sortKey="Prat, A" uniqKey="Prat A">A Prat</name>
</author>
<author><name sortKey="Tao, Jj" uniqKey="Tao J">JJ Tao</name>
</author>
<author><name sortKey="Spratt, De" uniqKey="Spratt D">DE Spratt</name>
</author>
<author><name sortKey="Viola Villegas, Nt" uniqKey="Viola Villegas N">NT Viola-Villegas</name>
</author>
<author><name sortKey="Castel, P" uniqKey="Castel P">P Castel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burrell, Ra" uniqKey="Burrell R">RA Burrell</name>
</author>
<author><name sortKey="Juul, N" uniqKey="Juul N">N Juul</name>
</author>
<author><name sortKey="Johnston, Sr" uniqKey="Johnston S">SR Johnston</name>
</author>
<author><name sortKey="Reis Filho, Js" uniqKey="Reis Filho J">JS Reis-Filho</name>
</author>
<author><name sortKey="Szallasi, Z" uniqKey="Szallasi Z">Z Szallasi</name>
</author>
<author><name sortKey="Swanton, C" uniqKey="Swanton C">C Swanton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Carter, Sl" uniqKey="Carter S">SL Carter</name>
</author>
<author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Helman, E" uniqKey="Helman E">E Helman</name>
</author>
<author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A McKenna</name>
</author>
<author><name sortKey="Shen, H" uniqKey="Shen H">H Shen</name>
</author>
<author><name sortKey="Zack, T" uniqKey="Zack T">T Zack</name>
</author>
<author><name sortKey="Laird, Pw" uniqKey="Laird P">PW Laird</name>
</author>
<author><name sortKey="Onofrio, Rc" uniqKey="Onofrio R">RC Onofrio</name>
</author>
<author><name sortKey="Winckler, W" uniqKey="Winckler W">W Winckler</name>
</author>
<author><name sortKey="Weir, Ba" uniqKey="Weir B">BA Weir</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cecener, G" uniqKey="Cecener G">G Cecener</name>
</author>
<author><name sortKey="Egeli, U" uniqKey="Egeli U">U Egeli</name>
</author>
<author><name sortKey="Tunca, B" uniqKey="Tunca B">B Tunca</name>
</author>
<author><name sortKey="Erturk, E" uniqKey="Erturk E">E Erturk</name>
</author>
<author><name sortKey="Ak, S" uniqKey="Ak S">S Ak</name>
</author>
<author><name sortKey="Gokgoz, S" uniqKey="Gokgoz S">S Gokgoz</name>
</author>
<author><name sortKey="Tasdelen, I" uniqKey="Tasdelen I">I Tasdelen</name>
</author>
<author><name sortKey="Tezcan, G" uniqKey="Tezcan G">G Tezcan</name>
</author>
<author><name sortKey="Demirdogen, E" uniqKey="Demirdogen E">E Demirdogen</name>
</author>
<author><name sortKey="Bayram, N" uniqKey="Bayram N">N Bayram</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cerami, E" uniqKey="Cerami E">E Cerami</name>
</author>
<author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
<author><name sortKey="Dogrusoz, U" uniqKey="Dogrusoz U">U Dogrusoz</name>
</author>
<author><name sortKey="Gross, Be" uniqKey="Gross B">BE Gross</name>
</author>
<author><name sortKey="Sumer, So" uniqKey="Sumer S">SO Sumer</name>
</author>
<author><name sortKey="Aksoy, Ba" uniqKey="Aksoy B">BA Aksoy</name>
</author>
<author><name sortKey="Jacobsen, A" uniqKey="Jacobsen A">A Jacobsen</name>
</author>
<author><name sortKey="Byrne, Cj" uniqKey="Byrne C">CJ Byrne</name>
</author>
<author><name sortKey="Heuer, Ml" uniqKey="Heuer M">ML Heuer</name>
</author>
<author><name sortKey="Larsson, E" uniqKey="Larsson E">E Larsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Lawrence, Ms" uniqKey="Lawrence M">MS Lawrence</name>
</author>
<author><name sortKey="Carter, Sl" uniqKey="Carter S">SL Carter</name>
</author>
<author><name sortKey="Sivachenko, A" uniqKey="Sivachenko A">A Sivachenko</name>
</author>
<author><name sortKey="Jaffe, D" uniqKey="Jaffe D">D Jaffe</name>
</author>
<author><name sortKey="Sougnez, C" uniqKey="Sougnez C">C Sougnez</name>
</author>
<author><name sortKey="Gabriel, S" uniqKey="Gabriel S">S Gabriel</name>
</author>
<author><name sortKey="Meyerson, M" uniqKey="Meyerson M">M Meyerson</name>
</author>
<author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name>
</author>
<author><name sortKey="Getz, G" uniqKey="Getz G">G Getz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cingolani, P" uniqKey="Cingolani P">P Cingolani</name>
</author>
<author><name sortKey="Platts, A" uniqKey="Platts A">A Platts</name>
</author>
<author><name sortKey="Wang Le, L" uniqKey="Wang Le L">L Wang Le</name>
</author>
<author><name sortKey="Coon, M" uniqKey="Coon M">M Coon</name>
</author>
<author><name sortKey="Nguyen, T" uniqKey="Nguyen T">T Nguyen</name>
</author>
<author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name>
</author>
<author><name sortKey="Land, Sj" uniqKey="Land S">SJ Land</name>
</author>
<author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name>
</author>
<author><name sortKey="Ruden, Dm" uniqKey="Ruden D">DM Ruden</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ciruelos Gil, Em" uniqKey="Ciruelos Gil E">EM Ciruelos Gil</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cox, Dg" uniqKey="Cox D">DG Cox</name>
</author>
<author><name sortKey="Hankinson, Se" uniqKey="Hankinson S">SE Hankinson</name>
</author>
<author><name sortKey="Hunter, Dj" uniqKey="Hunter D">DJ Hunter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dawson, Pj" uniqKey="Dawson P">PJ Dawson</name>
</author>
<author><name sortKey="Schroer, Kr" uniqKey="Schroer K">KR Schroer</name>
</author>
<author><name sortKey="Wolman, Sr" uniqKey="Wolman S">SR Wolman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Deb, S" uniqKey="Deb S">S Deb</name>
</author>
<author><name sortKey="Do, H" uniqKey="Do H">H Do</name>
</author>
<author><name sortKey="Byrne, D" uniqKey="Byrne D">D Byrne</name>
</author>
<author><name sortKey="Jene, N" uniqKey="Jene N">N Jene</name>
</author>
<author><name sortKey="Kconfab, I" uniqKey="Kconfab I">I kConFab</name>
</author>
<author><name sortKey="Dobrovic, A" uniqKey="Dobrovic A">A Dobrovic</name>
</author>
<author><name sortKey="Fox, Sb" uniqKey="Fox S">SB Fox</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Depristo, Ma" uniqKey="Depristo M">MA DePristo</name>
</author>
<author><name sortKey="Banks, E" uniqKey="Banks E">E Banks</name>
</author>
<author><name sortKey="Poplin, R" uniqKey="Poplin R">R Poplin</name>
</author>
<author><name sortKey="Garimella, Kv" uniqKey="Garimella K">KV Garimella</name>
</author>
<author><name sortKey="Maguire, Jr" uniqKey="Maguire J">JR Maguire</name>
</author>
<author><name sortKey="Hartl, C" uniqKey="Hartl C">C Hartl</name>
</author>
<author><name sortKey="Philippakis, Aa" uniqKey="Philippakis A">AA Philippakis</name>
</author>
<author><name sortKey="Del Angel, G" uniqKey="Del Angel G">G del Angel</name>
</author>
<author><name sortKey="Rivas, Ma" uniqKey="Rivas M">MA Rivas</name>
</author>
<author><name sortKey="Hanna, M" uniqKey="Hanna M">M Hanna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Efeyan, A" uniqKey="Efeyan A">A Efeyan</name>
</author>
<author><name sortKey="Sabatini, Dm" uniqKey="Sabatini D">DM Sabatini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Forbes, Sa" uniqKey="Forbes S">SA Forbes</name>
</author>
<author><name sortKey="Beare, D" uniqKey="Beare D">D Beare</name>
</author>
<author><name sortKey="Gunasekaran, P" uniqKey="Gunasekaran P">P Gunasekaran</name>
</author>
<author><name sortKey="Leung, K" uniqKey="Leung K">K Leung</name>
</author>
<author><name sortKey="Bindal, N" uniqKey="Bindal N">N Bindal</name>
</author>
<author><name sortKey="Boutselakis, H" uniqKey="Boutselakis H">H Boutselakis</name>
</author>
<author><name sortKey="Ding, M" uniqKey="Ding M">M Ding</name>
</author>
<author><name sortKey="Bamford, S" uniqKey="Bamford S">S Bamford</name>
</author>
<author><name sortKey="Cole, C" uniqKey="Cole C">C Cole</name>
</author>
<author><name sortKey="Ward, S" uniqKey="Ward S">S Ward</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
<author><name sortKey="Aksoy, Ba" uniqKey="Aksoy B">BA Aksoy</name>
</author>
<author><name sortKey="Dogrusoz, U" uniqKey="Dogrusoz U">U Dogrusoz</name>
</author>
<author><name sortKey="Dresdner, G" uniqKey="Dresdner G">G Dresdner</name>
</author>
<author><name sortKey="Gross, B" uniqKey="Gross B">B Gross</name>
</author>
<author><name sortKey="Sumer, So" uniqKey="Sumer S">SO Sumer</name>
</author>
<author><name sortKey="Sun, Y" uniqKey="Sun Y">Y Sun</name>
</author>
<author><name sortKey="Jacobsen, A" uniqKey="Jacobsen A">A Jacobsen</name>
</author>
<author><name sortKey="Sinha, R" uniqKey="Sinha R">R Sinha</name>
</author>
<author><name sortKey="Larsson, E" uniqKey="Larsson E">E Larsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name>
</author>
<author><name sortKey="Chen, D" uniqKey="Chen D">D Chen</name>
</author>
<author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
<author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name>
</author>
<author><name sortKey="Campone, M" uniqKey="Campone M">M Campone</name>
</author>
<author><name sortKey="Noguchi, S" uniqKey="Noguchi S">S Noguchi</name>
</author>
<author><name sortKey="Perez, A" uniqKey="Perez A">A Perez</name>
</author>
<author><name sortKey="Deleu, I" uniqKey="Deleu I">I Deleu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Janevski, A" uniqKey="Janevski A">A Janevski</name>
</author>
<author><name sortKey="Varadan, V" uniqKey="Varadan V">V Varadan</name>
</author>
<author><name sortKey="Kamalakaran, S" uniqKey="Kamalakaran S">S Kamalakaran</name>
</author>
<author><name sortKey="Banerjee, N" uniqKey="Banerjee N">N Banerjee</name>
</author>
<author><name sortKey="Dimitrova, N" uniqKey="Dimitrova N">N Dimitrova</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Juric, D" uniqKey="Juric D">D Juric</name>
</author>
<author><name sortKey="Baselga, J" uniqKey="Baselga J">J Baselga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name>
</author>
<author><name sortKey="Theodoropoulou, M" uniqKey="Theodoropoulou M">M Theodoropoulou</name>
</author>
<author><name sortKey="Graw, J" uniqKey="Graw J">J Graw</name>
</author>
<author><name sortKey="Roncaroli, F" uniqKey="Roncaroli F">F Roncaroli</name>
</author>
<author><name sortKey="Zatelli, Mc" uniqKey="Zatelli M">MC Zatelli</name>
</author>
<author><name sortKey="Pellegata, Ns" uniqKey="Pellegata N">NS Pellegata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Leung, Ey" uniqKey="Leung E">EY Leung</name>
</author>
<author><name sortKey="Askarian Amiri, M" uniqKey="Askarian Amiri M">M Askarian-Amiri</name>
</author>
<author><name sortKey="Finlay, Gj" uniqKey="Finlay G">GJ Finlay</name>
</author>
<author><name sortKey="Rewcastle, Gw" uniqKey="Rewcastle G">GW Rewcastle</name>
</author>
<author><name sortKey="Baguley, Bc" uniqKey="Baguley B">BC Baguley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name>
</author>
<author><name sortKey="Jian, X" uniqKey="Jian X">X Jian</name>
</author>
<author><name sortKey="Boerwinkle, E" uniqKey="Boerwinkle E">E Boerwinkle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Maira, Sm" uniqKey="Maira S">SM Maira</name>
</author>
<author><name sortKey="Stauffer, F" uniqKey="Stauffer F">F Stauffer</name>
</author>
<author><name sortKey="Brueggen, J" uniqKey="Brueggen J">J Brueggen</name>
</author>
<author><name sortKey="Furet, P" uniqKey="Furet P">P Furet</name>
</author>
<author><name sortKey="Schnell, C" uniqKey="Schnell C">C Schnell</name>
</author>
<author><name sortKey="Fritsch, C" uniqKey="Fritsch C">C Fritsch</name>
</author>
<author><name sortKey="Brachmann, S" uniqKey="Brachmann S">S Brachmann</name>
</author>
<author><name sortKey="Chene, P" uniqKey="Chene P">P Chene</name>
</author>
<author><name sortKey="De Pover, A" uniqKey="De Pover A">A De Pover</name>
</author>
<author><name sortKey="Schoemaker, K" uniqKey="Schoemaker K">K Schoemaker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A McKenna</name>
</author>
<author><name sortKey="Hanna, M" uniqKey="Hanna M">M Hanna</name>
</author>
<author><name sortKey="Banks, E" uniqKey="Banks E">E Banks</name>
</author>
<author><name sortKey="Sivachenko, A" uniqKey="Sivachenko A">A Sivachenko</name>
</author>
<author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Kernytsky, A" uniqKey="Kernytsky A">A Kernytsky</name>
</author>
<author><name sortKey="Garimella, K" uniqKey="Garimella K">K Garimella</name>
</author>
<author><name sortKey="Altshuler, D" uniqKey="Altshuler D">D Altshuler</name>
</author>
<author><name sortKey="Gabriel, S" uniqKey="Gabriel S">S Gabriel</name>
</author>
<author><name sortKey="Daly, M" uniqKey="Daly M">M Daly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nyfeler, B" uniqKey="Nyfeler B">B Nyfeler</name>
</author>
<author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name>
</author>
<author><name sortKey="Li, X" uniqKey="Li X">X Li</name>
</author>
<author><name sortKey="Pinzon Ortiz, M" uniqKey="Pinzon Ortiz M">M Pinzon-Ortiz</name>
</author>
<author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name>
</author>
<author><name sortKey="Reddy, A" uniqKey="Reddy A">A Reddy</name>
</author>
<author><name sortKey="Pradhan, E" uniqKey="Pradhan E">E Pradhan</name>
</author>
<author><name sortKey="Das, R" uniqKey="Das R">R Das</name>
</author>
<author><name sortKey="Lehar, J" uniqKey="Lehar J">J Lehar</name>
</author>
<author><name sortKey="Schlegel, R" uniqKey="Schlegel R">R Schlegel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ott, K" uniqKey="Ott K">K Ott</name>
</author>
<author><name sortKey="Vogelsang, H" uniqKey="Vogelsang H">H Vogelsang</name>
</author>
<author><name sortKey="Mueller, J" uniqKey="Mueller J">J Mueller</name>
</author>
<author><name sortKey="Becker, K" uniqKey="Becker K">K Becker</name>
</author>
<author><name sortKey="Muller, M" uniqKey="Muller M">M Muller</name>
</author>
<author><name sortKey="Fink, U" uniqKey="Fink U">U Fink</name>
</author>
<author><name sortKey="Siewert, Jr" uniqKey="Siewert J">JR Siewert</name>
</author>
<author><name sortKey="Hofler, H" uniqKey="Hofler H">H Hofler</name>
</author>
<author><name sortKey="Keller, G" uniqKey="Keller G">G Keller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Palli, D" uniqKey="Palli D">D Palli</name>
</author>
<author><name sortKey="Falchetti, M" uniqKey="Falchetti M">M Falchetti</name>
</author>
<author><name sortKey="Masala, G" uniqKey="Masala G">G Masala</name>
</author>
<author><name sortKey="Lupi, R" uniqKey="Lupi R">R Lupi</name>
</author>
<author><name sortKey="Sera, F" uniqKey="Sera F">F Sera</name>
</author>
<author><name sortKey="Saieva, C" uniqKey="Saieva C">C Saieva</name>
</author>
<author><name sortKey="D Amico, C" uniqKey="D Amico C">C D'Amico</name>
</author>
<author><name sortKey="Ceroti, M" uniqKey="Ceroti M">M Ceroti</name>
</author>
<author><name sortKey="Rizzolo, P" uniqKey="Rizzolo P">P Rizzolo</name>
</author>
<author><name sortKey="Caligo, Ma" uniqKey="Caligo M">MA Caligo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Passacantilli, I" uniqKey="Passacantilli I">I Passacantilli</name>
</author>
<author><name sortKey="Capurso, G" uniqKey="Capurso G">G Capurso</name>
</author>
<author><name sortKey="Archibugi, L" uniqKey="Archibugi L">L Archibugi</name>
</author>
<author><name sortKey="Calabretta, S" uniqKey="Calabretta S">S Calabretta</name>
</author>
<author><name sortKey="Caldarola, S" uniqKey="Caldarola S">S Caldarola</name>
</author>
<author><name sortKey="Loreni, F" uniqKey="Loreni F">F Loreni</name>
</author>
<author><name sortKey="Delle Fave, G" uniqKey="Delle Fave G">G Delle Fave</name>
</author>
<author><name sortKey="Sette, C" uniqKey="Sette C">C Sette</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name>
</author>
<author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name>
</author>
<author><name sortKey="Campone, M" uniqKey="Campone M">M Campone</name>
</author>
<author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name>
</author>
<author><name sortKey="Lebrun, F" uniqKey="Lebrun F">F Lebrun</name>
</author>
<author><name sortKey="Ito, Y" uniqKey="Ito Y">Y Ito</name>
</author>
<author><name sortKey="Noguchi, S" uniqKey="Noguchi S">S Noguchi</name>
</author>
<author><name sortKey="Perez, A" uniqKey="Perez A">A Perez</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Deleu, I" uniqKey="Deleu I">I Deleu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Robinson, Jt" uniqKey="Robinson J">JT Robinson</name>
</author>
<author><name sortKey="Thorvaldsdottir, H" uniqKey="Thorvaldsdottir H">H Thorvaldsdottir</name>
</author>
<author><name sortKey="Winckler, W" uniqKey="Winckler W">W Winckler</name>
</author>
<author><name sortKey="Guttman, M" uniqKey="Guttman M">M Guttman</name>
</author>
<author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name>
</author>
<author><name sortKey="Getz, G" uniqKey="Getz G">G Getz</name>
</author>
<author><name sortKey="Mesirov, Jp" uniqKey="Mesirov J">JP Mesirov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name>
</author>
<author><name sortKey="Downes, M" uniqKey="Downes M">M Downes</name>
</author>
<author><name sortKey="Xie, W" uniqKey="Xie W">W Xie</name>
</author>
<author><name sortKey="Kao, Hy" uniqKey="Kao H">HY Kao</name>
</author>
<author><name sortKey="Ordentlich, P" uniqKey="Ordentlich P">P Ordentlich</name>
</author>
<author><name sortKey="Tsai, Cc" uniqKey="Tsai C">CC Tsai</name>
</author>
<author><name sortKey="Hon, M" uniqKey="Hon M">M Hon</name>
</author>
<author><name sortKey="Evans, Rm" uniqKey="Evans R">RM Evans</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Thomas, He" uniqKey="Thomas H">HE Thomas</name>
</author>
<author><name sortKey="Mercer, Ca" uniqKey="Mercer C">CA Mercer</name>
</author>
<author><name sortKey="Carnevalli, Ls" uniqKey="Carnevalli L">LS Carnevalli</name>
</author>
<author><name sortKey="Park, J" uniqKey="Park J">J Park</name>
</author>
<author><name sortKey="Andersen, Jb" uniqKey="Andersen J">JB Andersen</name>
</author>
<author><name sortKey="Conner, Ea" uniqKey="Conner E">EA Conner</name>
</author>
<author><name sortKey="Tanaka, K" uniqKey="Tanaka K">K Tanaka</name>
</author>
<author><name sortKey="Matsutani, T" uniqKey="Matsutani T">T Matsutani</name>
</author>
<author><name sortKey="Iwanami, A" uniqKey="Iwanami A">A Iwanami</name>
</author>
<author><name sortKey="Aronow, Bj" uniqKey="Aronow B">BJ Aronow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xu, Cx" uniqKey="Xu C">CX Xu</name>
</author>
<author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name>
</author>
<author><name sortKey="Yue, P" uniqKey="Yue P">P Yue</name>
</author>
<author><name sortKey="Owonikoko, Tk" uniqKey="Owonikoko T">TK Owonikoko</name>
</author>
<author><name sortKey="Ramalingam, Ss" uniqKey="Ramalingam S">SS Ramalingam</name>
</author>
<author><name sortKey="Khuri, Fr" uniqKey="Khuri F">FR Khuri</name>
</author>
<author><name sortKey="Sun, Sy" uniqKey="Sun S">SY Sun</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xue, Wq" uniqKey="Xue W">WQ Xue</name>
</author>
<author><name sortKey="He, Yq" uniqKey="He Y">YQ He</name>
</author>
<author><name sortKey="Zhu, Jh" uniqKey="Zhu J">JH Zhu</name>
</author>
<author><name sortKey="Ma, Jq" uniqKey="Ma J">JQ Ma</name>
</author>
<author><name sortKey="He, J" uniqKey="He J">J He</name>
</author>
<author><name sortKey="Jia, Wh" uniqKey="Jia W">WH Jia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ye, K" uniqKey="Ye K">K Ye</name>
</author>
<author><name sortKey="Schulz, Mh" uniqKey="Schulz M">MH Schulz</name>
</author>
<author><name sortKey="Long, Q" uniqKey="Long Q">Q Long</name>
</author>
<author><name sortKey="Apweiler, R" uniqKey="Apweiler R">R Apweiler</name>
</author>
<author><name sortKey="Ning, Z" uniqKey="Ning Z">Z Ning</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
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<author><name sortKey="Patel, Parul" sort="Patel, Parul" uniqKey="Patel P" first="Parul" last="Patel">Parul Patel</name>
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</affiliation>
</author>
<author><name sortKey="Cheung, Wing" sort="Cheung, Wing" uniqKey="Cheung W" first="Wing" last="Cheung">Wing Cheung</name>
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<author><name sortKey="Morrissey, Michael" sort="Morrissey, Michael" uniqKey="Morrissey M" first="Michael" last="Morrissey">Michael Morrissey</name>
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</author>
<author><name sortKey="Carbone, Carmine" sort="Carbone, Carmine" uniqKey="Carbone C" first="Carmine" last="Carbone">Carmine Carbone</name>
<affiliation wicri:level="1"><nlm:aff id="af3">Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af6">Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona</wicri:regionArea>
<wicri:noRegion>37134 Verona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cottini, Silvia" sort="Cottini, Silvia" uniqKey="Cottini S" first="Silvia" last="Cottini">Silvia Cottini</name>
<affiliation wicri:level="1"><nlm:aff id="af2">Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3">Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tortora, Giampaolo" sort="Tortora, Giampaolo" uniqKey="Tortora G" first="Giampaolo" last="Tortora">Giampaolo Tortora</name>
<affiliation wicri:level="1"><nlm:aff id="af2">Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3">Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Melisi, Davide" sort="Melisi, Davide" uniqKey="Melisi D" first="Davide" last="Melisi">Davide Melisi</name>
<affiliation wicri:level="1"><nlm:aff id="af2">Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3">Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af6">Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona</wicri:regionArea>
<wicri:noRegion>37134 Verona</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Cold Spring Harbor Molecular Case Studies</title>
<idno type="ISSN">2373-2865</idno>
<idno type="eISSN">2373-2873</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER<sup>+</sup>
/HER2<sup>−</sup>
metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR<sup>+</sup>
)/HER2<sup>−</sup>
stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy. Upon the development of metastases, the patient began a 200 mg twice-daily BEZ235 and 2.5 mg weekly everolimus combination regimen. The patient sustained a prolonged stable disease of 18 mo while undergoing the therapy, before his tumor progressed again. Therefore, we sought to both better understand MBC and investigate the underlying molecular mechanisms of the patient's sensitivity and subsequent resistance to the BEZ235/everolimus combination therapy. Genomic and immunohistochemical analyses were performed on samples collected from the initial invasive ductal carcinoma pretreatment and a metastasis postprogression on the BEZ235/everolimus combination treatment. Both tumors were relatively quiet genomically with no overlap to recurrent MBC alterations in the literature. Markers of PI3K/mTOR pathway hyperactivation were not identified in the pretreatment sample, which complements previous reports of HR<sup>+</sup>
female breast cancers being responsive to mTOR inhibition without this activation. The postprogression sample, however, demonstrated greater than fivefold increased estrogen receptor and pathogenesis-related protein expression, which could have constrained the PI3K/mTOR pathway inhibition by BEZ235/everolimus. Overall, these analyses have augmented the limited episteme on MBC genetics and treatment.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="A Hern, Rp" uniqKey="A Hern R">RP A'Hern</name>
</author>
<author><name sortKey="Jamal Hanjani, M" uniqKey="Jamal Hanjani M">M Jamal-Hanjani</name>
</author>
<author><name sortKey="Szasz, Am" uniqKey="Szasz A">AM Szasz</name>
</author>
<author><name sortKey="Johnston, Sr" uniqKey="Johnston S">SR Johnston</name>
</author>
<author><name sortKey="Reis Filho, Js" uniqKey="Reis Filho J">JS Reis-Filho</name>
</author>
<author><name sortKey="Roylance, R" uniqKey="Roylance R">R Roylance</name>
</author>
<author><name sortKey="Swanton, C" uniqKey="Swanton C">C Swanton</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Baselga, J" uniqKey="Baselga J">J Baselga</name>
</author>
<author><name sortKey="Campone, M" uniqKey="Campone M">M Campone</name>
</author>
<author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name>
</author>
<author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Sahmoud, T" uniqKey="Sahmoud T">T Sahmoud</name>
</author>
<author><name sortKey="Noguchi, S" uniqKey="Noguchi S">S Noguchi</name>
</author>
<author><name sortKey="Gnant, M" uniqKey="Gnant M">M Gnant</name>
</author>
<author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name>
</author>
<author><name sortKey="Lebrun, F" uniqKey="Lebrun F">F Lebrun</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bendell, Jc" uniqKey="Bendell J">JC Bendell</name>
</author>
<author><name sortKey="Kurkjian, C" uniqKey="Kurkjian C">C Kurkjian</name>
</author>
<author><name sortKey="Infante, Jr" uniqKey="Infante J">JR Infante</name>
</author>
<author><name sortKey="Bauer, Tm" uniqKey="Bauer T">TM Bauer</name>
</author>
<author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
<author><name sortKey="Greco, Fa" uniqKey="Greco F">FA Greco</name>
</author>
<author><name sortKey="Shih, Kc" uniqKey="Shih K">KC Shih</name>
</author>
<author><name sortKey="Thompson, Ds" uniqKey="Thompson D">DS Thompson</name>
</author>
<author><name sortKey="Lane, Cm" uniqKey="Lane C">CM Lane</name>
</author>
<author><name sortKey="Finney, Lh" uniqKey="Finney L">LH Finney</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bosch, A" uniqKey="Bosch A">A Bosch</name>
</author>
<author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name>
</author>
<author><name sortKey="Bergamaschi, A" uniqKey="Bergamaschi A">A Bergamaschi</name>
</author>
<author><name sortKey="Ellis, H" uniqKey="Ellis H">H Ellis</name>
</author>
<author><name sortKey="Toska, E" uniqKey="Toska E">E Toska</name>
</author>
<author><name sortKey="Prat, A" uniqKey="Prat A">A Prat</name>
</author>
<author><name sortKey="Tao, Jj" uniqKey="Tao J">JJ Tao</name>
</author>
<author><name sortKey="Spratt, De" uniqKey="Spratt D">DE Spratt</name>
</author>
<author><name sortKey="Viola Villegas, Nt" uniqKey="Viola Villegas N">NT Viola-Villegas</name>
</author>
<author><name sortKey="Castel, P" uniqKey="Castel P">P Castel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burrell, Ra" uniqKey="Burrell R">RA Burrell</name>
</author>
<author><name sortKey="Juul, N" uniqKey="Juul N">N Juul</name>
</author>
<author><name sortKey="Johnston, Sr" uniqKey="Johnston S">SR Johnston</name>
</author>
<author><name sortKey="Reis Filho, Js" uniqKey="Reis Filho J">JS Reis-Filho</name>
</author>
<author><name sortKey="Szallasi, Z" uniqKey="Szallasi Z">Z Szallasi</name>
</author>
<author><name sortKey="Swanton, C" uniqKey="Swanton C">C Swanton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Carter, Sl" uniqKey="Carter S">SL Carter</name>
</author>
<author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Helman, E" uniqKey="Helman E">E Helman</name>
</author>
<author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A McKenna</name>
</author>
<author><name sortKey="Shen, H" uniqKey="Shen H">H Shen</name>
</author>
<author><name sortKey="Zack, T" uniqKey="Zack T">T Zack</name>
</author>
<author><name sortKey="Laird, Pw" uniqKey="Laird P">PW Laird</name>
</author>
<author><name sortKey="Onofrio, Rc" uniqKey="Onofrio R">RC Onofrio</name>
</author>
<author><name sortKey="Winckler, W" uniqKey="Winckler W">W Winckler</name>
</author>
<author><name sortKey="Weir, Ba" uniqKey="Weir B">BA Weir</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cecener, G" uniqKey="Cecener G">G Cecener</name>
</author>
<author><name sortKey="Egeli, U" uniqKey="Egeli U">U Egeli</name>
</author>
<author><name sortKey="Tunca, B" uniqKey="Tunca B">B Tunca</name>
</author>
<author><name sortKey="Erturk, E" uniqKey="Erturk E">E Erturk</name>
</author>
<author><name sortKey="Ak, S" uniqKey="Ak S">S Ak</name>
</author>
<author><name sortKey="Gokgoz, S" uniqKey="Gokgoz S">S Gokgoz</name>
</author>
<author><name sortKey="Tasdelen, I" uniqKey="Tasdelen I">I Tasdelen</name>
</author>
<author><name sortKey="Tezcan, G" uniqKey="Tezcan G">G Tezcan</name>
</author>
<author><name sortKey="Demirdogen, E" uniqKey="Demirdogen E">E Demirdogen</name>
</author>
<author><name sortKey="Bayram, N" uniqKey="Bayram N">N Bayram</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cerami, E" uniqKey="Cerami E">E Cerami</name>
</author>
<author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
<author><name sortKey="Dogrusoz, U" uniqKey="Dogrusoz U">U Dogrusoz</name>
</author>
<author><name sortKey="Gross, Be" uniqKey="Gross B">BE Gross</name>
</author>
<author><name sortKey="Sumer, So" uniqKey="Sumer S">SO Sumer</name>
</author>
<author><name sortKey="Aksoy, Ba" uniqKey="Aksoy B">BA Aksoy</name>
</author>
<author><name sortKey="Jacobsen, A" uniqKey="Jacobsen A">A Jacobsen</name>
</author>
<author><name sortKey="Byrne, Cj" uniqKey="Byrne C">CJ Byrne</name>
</author>
<author><name sortKey="Heuer, Ml" uniqKey="Heuer M">ML Heuer</name>
</author>
<author><name sortKey="Larsson, E" uniqKey="Larsson E">E Larsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Lawrence, Ms" uniqKey="Lawrence M">MS Lawrence</name>
</author>
<author><name sortKey="Carter, Sl" uniqKey="Carter S">SL Carter</name>
</author>
<author><name sortKey="Sivachenko, A" uniqKey="Sivachenko A">A Sivachenko</name>
</author>
<author><name sortKey="Jaffe, D" uniqKey="Jaffe D">D Jaffe</name>
</author>
<author><name sortKey="Sougnez, C" uniqKey="Sougnez C">C Sougnez</name>
</author>
<author><name sortKey="Gabriel, S" uniqKey="Gabriel S">S Gabriel</name>
</author>
<author><name sortKey="Meyerson, M" uniqKey="Meyerson M">M Meyerson</name>
</author>
<author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name>
</author>
<author><name sortKey="Getz, G" uniqKey="Getz G">G Getz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cingolani, P" uniqKey="Cingolani P">P Cingolani</name>
</author>
<author><name sortKey="Platts, A" uniqKey="Platts A">A Platts</name>
</author>
<author><name sortKey="Wang Le, L" uniqKey="Wang Le L">L Wang Le</name>
</author>
<author><name sortKey="Coon, M" uniqKey="Coon M">M Coon</name>
</author>
<author><name sortKey="Nguyen, T" uniqKey="Nguyen T">T Nguyen</name>
</author>
<author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name>
</author>
<author><name sortKey="Land, Sj" uniqKey="Land S">SJ Land</name>
</author>
<author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name>
</author>
<author><name sortKey="Ruden, Dm" uniqKey="Ruden D">DM Ruden</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ciruelos Gil, Em" uniqKey="Ciruelos Gil E">EM Ciruelos Gil</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cox, Dg" uniqKey="Cox D">DG Cox</name>
</author>
<author><name sortKey="Hankinson, Se" uniqKey="Hankinson S">SE Hankinson</name>
</author>
<author><name sortKey="Hunter, Dj" uniqKey="Hunter D">DJ Hunter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dawson, Pj" uniqKey="Dawson P">PJ Dawson</name>
</author>
<author><name sortKey="Schroer, Kr" uniqKey="Schroer K">KR Schroer</name>
</author>
<author><name sortKey="Wolman, Sr" uniqKey="Wolman S">SR Wolman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Deb, S" uniqKey="Deb S">S Deb</name>
</author>
<author><name sortKey="Do, H" uniqKey="Do H">H Do</name>
</author>
<author><name sortKey="Byrne, D" uniqKey="Byrne D">D Byrne</name>
</author>
<author><name sortKey="Jene, N" uniqKey="Jene N">N Jene</name>
</author>
<author><name sortKey="Kconfab, I" uniqKey="Kconfab I">I kConFab</name>
</author>
<author><name sortKey="Dobrovic, A" uniqKey="Dobrovic A">A Dobrovic</name>
</author>
<author><name sortKey="Fox, Sb" uniqKey="Fox S">SB Fox</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Depristo, Ma" uniqKey="Depristo M">MA DePristo</name>
</author>
<author><name sortKey="Banks, E" uniqKey="Banks E">E Banks</name>
</author>
<author><name sortKey="Poplin, R" uniqKey="Poplin R">R Poplin</name>
</author>
<author><name sortKey="Garimella, Kv" uniqKey="Garimella K">KV Garimella</name>
</author>
<author><name sortKey="Maguire, Jr" uniqKey="Maguire J">JR Maguire</name>
</author>
<author><name sortKey="Hartl, C" uniqKey="Hartl C">C Hartl</name>
</author>
<author><name sortKey="Philippakis, Aa" uniqKey="Philippakis A">AA Philippakis</name>
</author>
<author><name sortKey="Del Angel, G" uniqKey="Del Angel G">G del Angel</name>
</author>
<author><name sortKey="Rivas, Ma" uniqKey="Rivas M">MA Rivas</name>
</author>
<author><name sortKey="Hanna, M" uniqKey="Hanna M">M Hanna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Efeyan, A" uniqKey="Efeyan A">A Efeyan</name>
</author>
<author><name sortKey="Sabatini, Dm" uniqKey="Sabatini D">DM Sabatini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Forbes, Sa" uniqKey="Forbes S">SA Forbes</name>
</author>
<author><name sortKey="Beare, D" uniqKey="Beare D">D Beare</name>
</author>
<author><name sortKey="Gunasekaran, P" uniqKey="Gunasekaran P">P Gunasekaran</name>
</author>
<author><name sortKey="Leung, K" uniqKey="Leung K">K Leung</name>
</author>
<author><name sortKey="Bindal, N" uniqKey="Bindal N">N Bindal</name>
</author>
<author><name sortKey="Boutselakis, H" uniqKey="Boutselakis H">H Boutselakis</name>
</author>
<author><name sortKey="Ding, M" uniqKey="Ding M">M Ding</name>
</author>
<author><name sortKey="Bamford, S" uniqKey="Bamford S">S Bamford</name>
</author>
<author><name sortKey="Cole, C" uniqKey="Cole C">C Cole</name>
</author>
<author><name sortKey="Ward, S" uniqKey="Ward S">S Ward</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
<author><name sortKey="Aksoy, Ba" uniqKey="Aksoy B">BA Aksoy</name>
</author>
<author><name sortKey="Dogrusoz, U" uniqKey="Dogrusoz U">U Dogrusoz</name>
</author>
<author><name sortKey="Dresdner, G" uniqKey="Dresdner G">G Dresdner</name>
</author>
<author><name sortKey="Gross, B" uniqKey="Gross B">B Gross</name>
</author>
<author><name sortKey="Sumer, So" uniqKey="Sumer S">SO Sumer</name>
</author>
<author><name sortKey="Sun, Y" uniqKey="Sun Y">Y Sun</name>
</author>
<author><name sortKey="Jacobsen, A" uniqKey="Jacobsen A">A Jacobsen</name>
</author>
<author><name sortKey="Sinha, R" uniqKey="Sinha R">R Sinha</name>
</author>
<author><name sortKey="Larsson, E" uniqKey="Larsson E">E Larsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name>
</author>
<author><name sortKey="Chen, D" uniqKey="Chen D">D Chen</name>
</author>
<author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Burris, Ha" uniqKey="Burris H">HA Burris</name>
</author>
<author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name>
</author>
<author><name sortKey="Campone, M" uniqKey="Campone M">M Campone</name>
</author>
<author><name sortKey="Noguchi, S" uniqKey="Noguchi S">S Noguchi</name>
</author>
<author><name sortKey="Perez, A" uniqKey="Perez A">A Perez</name>
</author>
<author><name sortKey="Deleu, I" uniqKey="Deleu I">I Deleu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Janevski, A" uniqKey="Janevski A">A Janevski</name>
</author>
<author><name sortKey="Varadan, V" uniqKey="Varadan V">V Varadan</name>
</author>
<author><name sortKey="Kamalakaran, S" uniqKey="Kamalakaran S">S Kamalakaran</name>
</author>
<author><name sortKey="Banerjee, N" uniqKey="Banerjee N">N Banerjee</name>
</author>
<author><name sortKey="Dimitrova, N" uniqKey="Dimitrova N">N Dimitrova</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Juric, D" uniqKey="Juric D">D Juric</name>
</author>
<author><name sortKey="Baselga, J" uniqKey="Baselga J">J Baselga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name>
</author>
<author><name sortKey="Theodoropoulou, M" uniqKey="Theodoropoulou M">M Theodoropoulou</name>
</author>
<author><name sortKey="Graw, J" uniqKey="Graw J">J Graw</name>
</author>
<author><name sortKey="Roncaroli, F" uniqKey="Roncaroli F">F Roncaroli</name>
</author>
<author><name sortKey="Zatelli, Mc" uniqKey="Zatelli M">MC Zatelli</name>
</author>
<author><name sortKey="Pellegata, Ns" uniqKey="Pellegata N">NS Pellegata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Leung, Ey" uniqKey="Leung E">EY Leung</name>
</author>
<author><name sortKey="Askarian Amiri, M" uniqKey="Askarian Amiri M">M Askarian-Amiri</name>
</author>
<author><name sortKey="Finlay, Gj" uniqKey="Finlay G">GJ Finlay</name>
</author>
<author><name sortKey="Rewcastle, Gw" uniqKey="Rewcastle G">GW Rewcastle</name>
</author>
<author><name sortKey="Baguley, Bc" uniqKey="Baguley B">BC Baguley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name>
</author>
<author><name sortKey="Jian, X" uniqKey="Jian X">X Jian</name>
</author>
<author><name sortKey="Boerwinkle, E" uniqKey="Boerwinkle E">E Boerwinkle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Maira, Sm" uniqKey="Maira S">SM Maira</name>
</author>
<author><name sortKey="Stauffer, F" uniqKey="Stauffer F">F Stauffer</name>
</author>
<author><name sortKey="Brueggen, J" uniqKey="Brueggen J">J Brueggen</name>
</author>
<author><name sortKey="Furet, P" uniqKey="Furet P">P Furet</name>
</author>
<author><name sortKey="Schnell, C" uniqKey="Schnell C">C Schnell</name>
</author>
<author><name sortKey="Fritsch, C" uniqKey="Fritsch C">C Fritsch</name>
</author>
<author><name sortKey="Brachmann, S" uniqKey="Brachmann S">S Brachmann</name>
</author>
<author><name sortKey="Chene, P" uniqKey="Chene P">P Chene</name>
</author>
<author><name sortKey="De Pover, A" uniqKey="De Pover A">A De Pover</name>
</author>
<author><name sortKey="Schoemaker, K" uniqKey="Schoemaker K">K Schoemaker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A McKenna</name>
</author>
<author><name sortKey="Hanna, M" uniqKey="Hanna M">M Hanna</name>
</author>
<author><name sortKey="Banks, E" uniqKey="Banks E">E Banks</name>
</author>
<author><name sortKey="Sivachenko, A" uniqKey="Sivachenko A">A Sivachenko</name>
</author>
<author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Kernytsky, A" uniqKey="Kernytsky A">A Kernytsky</name>
</author>
<author><name sortKey="Garimella, K" uniqKey="Garimella K">K Garimella</name>
</author>
<author><name sortKey="Altshuler, D" uniqKey="Altshuler D">D Altshuler</name>
</author>
<author><name sortKey="Gabriel, S" uniqKey="Gabriel S">S Gabriel</name>
</author>
<author><name sortKey="Daly, M" uniqKey="Daly M">M Daly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nyfeler, B" uniqKey="Nyfeler B">B Nyfeler</name>
</author>
<author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name>
</author>
<author><name sortKey="Li, X" uniqKey="Li X">X Li</name>
</author>
<author><name sortKey="Pinzon Ortiz, M" uniqKey="Pinzon Ortiz M">M Pinzon-Ortiz</name>
</author>
<author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name>
</author>
<author><name sortKey="Reddy, A" uniqKey="Reddy A">A Reddy</name>
</author>
<author><name sortKey="Pradhan, E" uniqKey="Pradhan E">E Pradhan</name>
</author>
<author><name sortKey="Das, R" uniqKey="Das R">R Das</name>
</author>
<author><name sortKey="Lehar, J" uniqKey="Lehar J">J Lehar</name>
</author>
<author><name sortKey="Schlegel, R" uniqKey="Schlegel R">R Schlegel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ott, K" uniqKey="Ott K">K Ott</name>
</author>
<author><name sortKey="Vogelsang, H" uniqKey="Vogelsang H">H Vogelsang</name>
</author>
<author><name sortKey="Mueller, J" uniqKey="Mueller J">J Mueller</name>
</author>
<author><name sortKey="Becker, K" uniqKey="Becker K">K Becker</name>
</author>
<author><name sortKey="Muller, M" uniqKey="Muller M">M Muller</name>
</author>
<author><name sortKey="Fink, U" uniqKey="Fink U">U Fink</name>
</author>
<author><name sortKey="Siewert, Jr" uniqKey="Siewert J">JR Siewert</name>
</author>
<author><name sortKey="Hofler, H" uniqKey="Hofler H">H Hofler</name>
</author>
<author><name sortKey="Keller, G" uniqKey="Keller G">G Keller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Palli, D" uniqKey="Palli D">D Palli</name>
</author>
<author><name sortKey="Falchetti, M" uniqKey="Falchetti M">M Falchetti</name>
</author>
<author><name sortKey="Masala, G" uniqKey="Masala G">G Masala</name>
</author>
<author><name sortKey="Lupi, R" uniqKey="Lupi R">R Lupi</name>
</author>
<author><name sortKey="Sera, F" uniqKey="Sera F">F Sera</name>
</author>
<author><name sortKey="Saieva, C" uniqKey="Saieva C">C Saieva</name>
</author>
<author><name sortKey="D Amico, C" uniqKey="D Amico C">C D'Amico</name>
</author>
<author><name sortKey="Ceroti, M" uniqKey="Ceroti M">M Ceroti</name>
</author>
<author><name sortKey="Rizzolo, P" uniqKey="Rizzolo P">P Rizzolo</name>
</author>
<author><name sortKey="Caligo, Ma" uniqKey="Caligo M">MA Caligo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Passacantilli, I" uniqKey="Passacantilli I">I Passacantilli</name>
</author>
<author><name sortKey="Capurso, G" uniqKey="Capurso G">G Capurso</name>
</author>
<author><name sortKey="Archibugi, L" uniqKey="Archibugi L">L Archibugi</name>
</author>
<author><name sortKey="Calabretta, S" uniqKey="Calabretta S">S Calabretta</name>
</author>
<author><name sortKey="Caldarola, S" uniqKey="Caldarola S">S Caldarola</name>
</author>
<author><name sortKey="Loreni, F" uniqKey="Loreni F">F Loreni</name>
</author>
<author><name sortKey="Delle Fave, G" uniqKey="Delle Fave G">G Delle Fave</name>
</author>
<author><name sortKey="Sette, C" uniqKey="Sette C">C Sette</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name>
</author>
<author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name>
</author>
<author><name sortKey="Campone, M" uniqKey="Campone M">M Campone</name>
</author>
<author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name>
</author>
<author><name sortKey="Lebrun, F" uniqKey="Lebrun F">F Lebrun</name>
</author>
<author><name sortKey="Ito, Y" uniqKey="Ito Y">Y Ito</name>
</author>
<author><name sortKey="Noguchi, S" uniqKey="Noguchi S">S Noguchi</name>
</author>
<author><name sortKey="Perez, A" uniqKey="Perez A">A Perez</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Deleu, I" uniqKey="Deleu I">I Deleu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Robinson, Jt" uniqKey="Robinson J">JT Robinson</name>
</author>
<author><name sortKey="Thorvaldsdottir, H" uniqKey="Thorvaldsdottir H">H Thorvaldsdottir</name>
</author>
<author><name sortKey="Winckler, W" uniqKey="Winckler W">W Winckler</name>
</author>
<author><name sortKey="Guttman, M" uniqKey="Guttman M">M Guttman</name>
</author>
<author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name>
</author>
<author><name sortKey="Getz, G" uniqKey="Getz G">G Getz</name>
</author>
<author><name sortKey="Mesirov, Jp" uniqKey="Mesirov J">JP Mesirov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name>
</author>
<author><name sortKey="Downes, M" uniqKey="Downes M">M Downes</name>
</author>
<author><name sortKey="Xie, W" uniqKey="Xie W">W Xie</name>
</author>
<author><name sortKey="Kao, Hy" uniqKey="Kao H">HY Kao</name>
</author>
<author><name sortKey="Ordentlich, P" uniqKey="Ordentlich P">P Ordentlich</name>
</author>
<author><name sortKey="Tsai, Cc" uniqKey="Tsai C">CC Tsai</name>
</author>
<author><name sortKey="Hon, M" uniqKey="Hon M">M Hon</name>
</author>
<author><name sortKey="Evans, Rm" uniqKey="Evans R">RM Evans</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Thomas, He" uniqKey="Thomas H">HE Thomas</name>
</author>
<author><name sortKey="Mercer, Ca" uniqKey="Mercer C">CA Mercer</name>
</author>
<author><name sortKey="Carnevalli, Ls" uniqKey="Carnevalli L">LS Carnevalli</name>
</author>
<author><name sortKey="Park, J" uniqKey="Park J">J Park</name>
</author>
<author><name sortKey="Andersen, Jb" uniqKey="Andersen J">JB Andersen</name>
</author>
<author><name sortKey="Conner, Ea" uniqKey="Conner E">EA Conner</name>
</author>
<author><name sortKey="Tanaka, K" uniqKey="Tanaka K">K Tanaka</name>
</author>
<author><name sortKey="Matsutani, T" uniqKey="Matsutani T">T Matsutani</name>
</author>
<author><name sortKey="Iwanami, A" uniqKey="Iwanami A">A Iwanami</name>
</author>
<author><name sortKey="Aronow, Bj" uniqKey="Aronow B">BJ Aronow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xu, Cx" uniqKey="Xu C">CX Xu</name>
</author>
<author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name>
</author>
<author><name sortKey="Yue, P" uniqKey="Yue P">P Yue</name>
</author>
<author><name sortKey="Owonikoko, Tk" uniqKey="Owonikoko T">TK Owonikoko</name>
</author>
<author><name sortKey="Ramalingam, Ss" uniqKey="Ramalingam S">SS Ramalingam</name>
</author>
<author><name sortKey="Khuri, Fr" uniqKey="Khuri F">FR Khuri</name>
</author>
<author><name sortKey="Sun, Sy" uniqKey="Sun S">SY Sun</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xue, Wq" uniqKey="Xue W">WQ Xue</name>
</author>
<author><name sortKey="He, Yq" uniqKey="He Y">YQ He</name>
</author>
<author><name sortKey="Zhu, Jh" uniqKey="Zhu J">JH Zhu</name>
</author>
<author><name sortKey="Ma, Jq" uniqKey="Ma J">JQ Ma</name>
</author>
<author><name sortKey="He, J" uniqKey="He J">J He</name>
</author>
<author><name sortKey="Jia, Wh" uniqKey="Jia W">WH Jia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ye, K" uniqKey="Ye K">K Ye</name>
</author>
<author><name sortKey="Schulz, Mh" uniqKey="Schulz M">MH Schulz</name>
</author>
<author><name sortKey="Long, Q" uniqKey="Long Q">Q Long</name>
</author>
<author><name sortKey="Apweiler, R" uniqKey="Apweiler R">R Apweiler</name>
</author>
<author><name sortKey="Ning, Z" uniqKey="Ning Z">Z Ning</name>
</author>
</analytic>
</biblStruct>
</listBibl>
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<author><name sortKey="Cheung, Wing" sort="Cheung, Wing" uniqKey="Cheung W" first="Wing" last="Cheung">Wing Cheung</name>
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<author><name sortKey="Morrissey, Michael" sort="Morrissey, Michael" uniqKey="Morrissey M" first="Michael" last="Morrissey">Michael Morrissey</name>
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<author><name sortKey="Carbone, Carmine" sort="Carbone, Carmine" uniqKey="Carbone C" first="Carmine" last="Carbone">Carmine Carbone</name>
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</author>
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</affiliation>
</author>
<author><name sortKey="Chen, David" sort="Chen, David" uniqKey="Chen D" first="David" last="Chen">David Chen</name>
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</affiliation>
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<author><name sortKey="Hummel, Jennifer" sort="Hummel, Jennifer" uniqKey="Hummel J" first="Jennifer" last="Hummel">Jennifer Hummel</name>
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<wicri:regionArea>Genoptix, Inc., Carlsbad, California 92008</wicri:regionArea>
<wicri:noRegion>California 92008</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gallo, Jorge" sort="Gallo, Jorge" uniqKey="Gallo J" first="Jorge" last="Gallo">Jorge Gallo</name>
<affiliation wicri:level="1"><nlm:affiliation>Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA;</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936</wicri:regionArea>
<wicri:noRegion>New Jersey 07936</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Riester, Markus" sort="Riester, Markus" uniqKey="Riester M" first="Markus" last="Riester">Markus Riester</name>
<affiliation wicri:level="1"><nlm:affiliation>Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA;</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139</wicri:regionArea>
<wicri:noRegion>Massachusetts 02139</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Patel, Parul" sort="Patel, Parul" uniqKey="Patel P" first="Parul" last="Patel">Parul Patel</name>
<affiliation wicri:level="1"><nlm:affiliation>Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA;</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936</wicri:regionArea>
<wicri:noRegion>New Jersey 07936</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cheung, Wing" sort="Cheung, Wing" uniqKey="Cheung W" first="Wing" last="Cheung">Wing Cheung</name>
<affiliation wicri:level="1"><nlm:affiliation>Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA;</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936</wicri:regionArea>
<wicri:noRegion>New Jersey 07936</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Morrissey, Michael" sort="Morrissey, Michael" uniqKey="Morrissey M" first="Michael" last="Morrissey">Michael Morrissey</name>
<affiliation wicri:level="1"><nlm:affiliation>Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA;</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139</wicri:regionArea>
<wicri:noRegion>Massachusetts 02139</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Carbone, Carmine" sort="Carbone, Carmine" uniqKey="Carbone C" first="Carmine" last="Carbone">Carmine Carbone</name>
<affiliation wicri:level="1"><nlm:affiliation>Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona</wicri:regionArea>
<wicri:noRegion>37134 Verona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cottini, Silvia" sort="Cottini, Silvia" uniqKey="Cottini S" first="Silvia" last="Cottini">Silvia Cottini</name>
<affiliation wicri:level="1"><nlm:affiliation>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tortora, Giampaolo" sort="Tortora, Giampaolo" uniqKey="Tortora G" first="Giampaolo" last="Tortora">Giampaolo Tortora</name>
<affiliation wicri:level="1"><nlm:affiliation>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona</wicri:regionArea>
<wicri:noRegion>37126 Verona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Melisi, Davide" sort="Melisi, Davide" uniqKey="Melisi D" first="Davide" last="Melisi">Davide Melisi</name>
<affiliation wicri:level="1"><nlm:affiliation>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Comprehensive Cancer Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy;; Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, 37134 Verona</wicri:regionArea>
<wicri:noRegion>37134 Verona</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Cold Spring Harbor molecular case studies</title>
<idno type="ISSN">2373-2865</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en">The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER(+)/HER2(-) metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR(+))/HER2(-) stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy. Upon the development of metastases, the patient began a 200 mg twice-daily BEZ235 and 2.5 mg weekly everolimus combination regimen. The patient sustained a prolonged stable disease of 18 mo while undergoing the therapy, before his tumor progressed again. Therefore, we sought to both better understand MBC and investigate the underlying molecular mechanisms of the patient's sensitivity and subsequent resistance to the BEZ235/everolimus combination therapy. Genomic and immunohistochemical analyses were performed on samples collected from the initial invasive ductal carcinoma pretreatment and a metastasis postprogression on the BEZ235/everolimus combination treatment. Both tumors were relatively quiet genomically with no overlap to recurrent MBC alterations in the literature. Markers of PI3K/mTOR pathway hyperactivation were not identified in the pretreatment sample, which complements previous reports of HR(+) female breast cancers being responsive to mTOR inhibition without this activation. The postprogression sample, however, demonstrated greater than fivefold increased estrogen receptor and pathogenesis-related protein expression, which could have constrained the PI3K/mTOR pathway inhibition by BEZ235/everolimus. Overall, these analyses have augmented the limited episteme on MBC genetics and treatment.</div>
</front>
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